title: Favipiravir (T-705), a novel viral RNA polymerase inhibitor.
abstract: Favipiravir (T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) is an antiviral drug that selectively inhibits the RNA-dependent RNA polymerase of influenza virus. It is phosphoribosylated by cellular enzymes to its active form, favipiravir-ribofuranosyl-5'-triphosphate (RTP). Its antiviral effect is attenuated by the addition of purine nucleic acids, indicating the viral RNA polymerase mistakenly recognizes favipiravir-RTP as a purine nucleotide. Favipiravir is active against a broad range of influenza viruses, including A(H1N1)pdm09, A(H5N1) and the recently emerged A(H7N9) avian virus. It also inhibits influenza strains resistant to current antiviral drugs, and shows a synergistic effect in combination with oseltamivir, thereby expanding influenza treatment options. A Phase III clinical evaluation of favipiravir for influenza therapy has been completed in Japan and two Phase II studies have been completed in the United States. In addition to its anti-influenza activity, favipiravir blocks the replication of many other RNA viruses, including arenaviruses (Junin, Machupo and Pichinde); phleboviruses (Rift Valley fever, sandfly fever and Punta Toro); hantaviruses (Maporal, Dobrava, and Prospect Hill); flaviviruses (yellow fever and West Nile); enteroviruses (polio- and rhinoviruses); an alphavirus, Western equine encephalitis virus; a paramyxovirus, respiratory syncytial virus; and noroviruses. With its unique mechanism of action and broad range of antiviral activity, favipiravir is a promising drug candidate for influenza and many other RNA viral diseases for which there are no approved therapies.
authors.affiliation: Toyama Chemical Co., Ltd., 4-1, Shimookui 2-chome, Toyama 930-8508, Japan. Electronic address: yousuke_furuta@toyama-chemical.co.jp.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Furuta
authors.forename: Brian B
authors.initials: BB
authors.lastname: Gowen
authors.forename: Kazumi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Kimiyasu
authors.initials: K
authors.lastname: Shiraki
authors.forename: Donald F
authors.initials: DF
authors.lastname: Smee
authors.forename: Dale L
authors.initials: DL
authors.lastname: Barnard
mesh_terms: D000577:Amides / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy*; D007564:Japan; D011719:Pyrazines / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D012328:RNA Viruses / Q000187:drug effects*; D014481:United States
chemical_list: D000577:Amides; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D011719:Pyrazines; D012321:DNA-Directed RNA Polymerases; C462182:favipiravir
keywords: Favipiravir; Influenza; RNA viruses; RNA-dependent RNA polymerase; T-705